Hirad Adnan A, Mix Doran, Venkataraman Arun, Meyers Steven P, Mahon Bradford Z
Department of Surgery, University of Rochester Medical Center, Rochester, NY, 1462, USA.
Department of Neuroscience, University of Rochester Medical Center, Rochester, NY 14642, USA.
bioRxiv. 2024 May 23:2024.05.22.595352. doi: 10.1101/2024.05.22.595352.
Brain tissue injury caused by mild traumatic brain injury (mTBI) disproportionately concentrates in the midbrain, cerebellum, mesial temporal lobe, and the interface between cortex and white matter at sulcal depths . The bio-mechanical principles that explain why physical impacts to different parts of the skull translate to common foci of injury concentrated in specific brain structures are unknown. A general and longstanding idea, which has not to date been directly tested in humans, is that different brain regions are differentially susceptible to strain loading. We use Magnetic Resonance Elastography (MRE) in healthy participants to develop whole-brain bio-mechanical vulnerability maps that independently define which regions of the brain exhibit disproportionate strain concentration. We then validate those vulnerability maps in a prospective cohort of mTBI patients, using diffusion MRI data collected at three cross-sectional timepoints after injury: acute, sub-acute, chronic. We show that regions that exhibit high strain, measured with MRE, are also the sites of greatest injury, as measured with diffusion MR in mTBI patients. This was the case in acute, subacute, and chronic subgroups of the mTBI cohort. Follow-on analyses decomposed the biomechanical cause of increased strain by showing it is caused jointly by disproportionately higher levels of energy arriving to 'high-strain' structures, as well as the inability of 'high strain' structures to effectively disperse that energy. These findings establish a causal mechanism that explains the anatomy of injury in mTBI based on rheological properties of the human brain.
轻度创伤性脑损伤（mTBI）所致的脑组织损伤不成比例地集中于中脑、小脑、颞叶内侧以及脑沟深处皮质与白质的交界处。目前尚不清楚何种生物力学原理能够解释为何颅骨不同部位受到的物理撞击会转化为集中于特定脑结构的常见损伤灶。一个长期以来的普遍观点认为，不同脑区对应变负荷的易感性存在差异，但迄今为止尚未在人体中得到直接验证。我们对健康受试者使用磁共振弹性成像（MRE）技术来绘制全脑生物力学易损性图谱，从而独立确定哪些脑区会出现不成比例的应变集中。随后，我们在一个mTBI患者前瞻性队列中验证这些易损性图谱，利用在损伤后三个横断面时间点（急性、亚急性、慢性）收集的扩散MRI数据。我们发现，用MRE测量显示高应变的区域，在用扩散MRI测量时也是mTBI患者中损伤最严重的部位。在mTBI队列的急性、亚急性和慢性亚组中均是如此。后续分析通过表明应变增加的生物力学原因是由到达“高应变”结构的能量水平不成比例地更高以及“高应变”结构无法有效分散该能量共同导致的，从而分解了应变增加的生物力学原因。这些发现建立了一种因果机制，基于人脑的流变学特性解释了mTBI中的损伤解剖结构。
